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Enalapril

Klassificering: C

Preparat: Enalapril Actavis, Enalapril Alpharma, Enalapril Astimex, Enalapril comp ratiopharm, Enalapril Comp Sandoz, Enalapril Comp STADA®, Enalapril Copyfarm, Enalapril Durascan, Enalapril Krka, Enalapril Mylan, Enalapril Orion, Enalapril Ranbaxy, Enalapril ratiopharm, Enalapril Sandoz, Enalapril STADA®, Enalapril Teva, Enalapril Vitabalans, Enalapril/Hydrochlorothiazide 2care4, Enalapril/Hydrochlorothiazide Mylan, Enalapril/Hydrochlorothiazide Orion, Enalapril/Hydrochlorothiazide Teva, Enap, Linatil, Linatil comp, Linatil comp mite, Renitec®, Renitec® comp., Synerpril®

ATC kod: C09AA02, C09BA02

Substanser: enalapril, enalaprilat, enalaprilmaleat

Sammanfattning

Det finns inga kliniskt relevanta könsskillnader i farmakokinetik eller i effekt av enalapril beskrivna. Hosta är en vanlig icke-dosberoende biverkan av ACE-hämmare och förekommer oftare hos kvinnor. Angiotensinreceptorblockerare kan då vara ett alternativ.

Additional information

Pharmacokinetics and dosing

No studies with a clinically relevant sex analysis regarding the pharmacokinetics of enalapril have been found. In a clinical study involving 110 hypertensive pediatric patients 6-16 years of age, the dose-dependent antihypertensive efficacy of enalapril was similar in boys and girls [12].

Effects

A small clinical trial (10 boys, 12 girls) has shown that adolescent girls with type 1 diabetes mellitus respond more favorably to ACE inhibitors than adolescent boys. Glomerular hyperfiltration is a factor for development of diabetic renal disease, and is influenced by hyperglycemia and RAS blockade. Twenty-two adolescents with type 1 diabetes mellitus were studied before and after ACE inhibition. After 21 days of treatment with enalapril (0.1 mg/kg daily x 1 week and then 0.1 mg/kg twice a day for 2 weeks), the renal responses to ACE inhibition differed between boys and girls . Only girls received beneficial reductions in GFR (glomerular filtration rate) and FF (filtration fraction). This may be due to a synergistic effect of ACE inhibitors and estrogen on components of the RAS. Even though the experiments in this study were carried out during the follicular (low estrogen) phase of the menstrual cycle, an augmented response to ACE inhibitors were noted in girls, suggesting that any levels of estrogen may act synergistically with RAS blockade [13]. An interaction between ACE inhibitors and estrogen has also been discussed [14].

A randomized controlled trial (46 men, 37 women) studied long-term effects of enalapril on plasma levels of the fibrinolytic factors tissue plasminogen activator (tPa), plasminogen activator inhibitor (PAI-1), tPA/PAI-1 complex and vWF in both sexes with uncomplicated myocardial infarction. Enalapril or placebo was initiated two months or later following an acute myocardial infarction. Initial dose was 2.5 mg enalapril once daily with increasing dosage every three days. Plasma levels of tPA decreased significantly after two weeks enalapril treatment in both sexes, but tPa/PAI-1 complex decreased significantly only in women [15].

Adverse effects

Several studies have reported a female predominance in the prevalence of ACE inhibitor induced cough [1-9]. The pathogenesis of the cough reaction is unknown. Different threshold for coughing in men and women have been proposed [10], as well as ethnic differences in cough tendency [11]. One study suggests that sex hormones do not have any influence on cough, since most of the women in the study were postmenopausal [1].In a double-blind placebo-controlled study (SOLVD), adverse effects of enalapril analyzed (5794 men, 975 women). The most pronounced sex difference among reported side effects in the enalapril group was cough, which was more frequently reported by women (10.0% vs. 4.2%; odds ratio 2.38) [3].A review has examined ACE inhibitor-associated angioedema/urticaria; the number of reports among patients taking enalapril (mean dose 13 mg daily) were 13/11841 men and 10/13672 women [16].

Drug interactions

Swedish users, please consult Janusmed Interactions (Janusmed interaktioner).

Birth defects

Enalapril should not be used in pregnant women. Swedish users, please consultJanusmed Drugs and Birth Defects (Janusmed fosterpåverkan).

Försäljning på recept

Fler män än kvinnor hämtade ut tabletter innehållande enalapril (ATC-kod C09AA02) på recept i Sverige år 2015, totalt 253 505 män och 208 910 kvinnor. Det motsvarar 52 respektive 43 personer per tusen invånare. Andelen som hämtat ut läkemedel ökade med stigande ålder hos båda könen. I genomsnitt var tabletter innehållande enalapril 1,4 gånger vanligare hos män [17].

Fler män än kvinnor hämtade ut tabletter innehållande kombination av enalapril och hydroklortiazid (ATC-kod C09BA02) på recept i Sverige år 2015, totalt 51 788 män och 35 480 kvinnor. Det motsvarar 11 respektive 7 personer per tusen invånare. Andelen som hämtat ut läkemedel var högst i åldersgruppen 70-79 år hos män och i åldersgruppen 75-84 år hos kvinnor. I genomsnitt var tabletter innehållande kombination av enalapril och hydroklortiazid 2,1 gånger vanligare hos män [17].

Uppdaterat: 2017-03-28

Litteratursökningsdatum: 2013-10-28

Referenser

  1. Coulter DM, Edwards IR. Cough associated with captopril and enalapril. Br Med J (Clin Res Ed). 1987;294:1521-3. PubMed
  2. Strocchi E, Valtancoli G, Ambrosioni E. The incidence of cough during treatment with angiotensin converting enzyme inhibitors. J Hypertens Suppl. 1989;7:S308-9. PubMed
  3. Kostis JB, Shelton B, Gosselin G, Goulet C, Hood WB, Kohn RM et al. Adverse effects of enalapril in the Studies of Left Ventricular Dysfunction (SOLVD) SOLVD Investigators. Am Heart J. 1996;131:350-5. PubMed
  4. Sharma S, Gupta U, Bapna JS, Sahai A. Tolerability of enalapril in mild to moderate hypertension. J Assoc Physicians India. 1995;43:475-6. PubMed
  5. Yeşil S, Yeşil M, Bayata S, Postaci N. ACE inhibitors and cough. Angiology. 1994;45:805-8. PubMed
  6. Yeo WW, Ramsay LE. Persistent dry cough with enalapril: incidence depends on method used. J Hum Hypertens. 1990;4:517-20. PubMed
  7. Just PM. The positive association of cough with angiotensin-converting enzyme inhibitors. Pharmacotherapy. 1989;9:82-7. PubMed
  8. Gibson GR. Enalapril-induced cough. Arch Intern Med. 1989;149:2701-3. PubMed
  9. Os I, Bratland B, Dahlöf B, Gisholt K, Syvertsen JO, Tretli S. Female sex as an important determinant of lisinopril-induced cough. Lancet. 1992;339:372. PubMed
  10. Dykewicz MS. Cough and angioedema from angiotensin-converting enzyme inhibitors: new insights into mechanisms and management. Curr Opin Allergy Clin Immunol. 2004;4:267-70. PubMed
  11. Morimoto T, Gandhi TK, Fiskio JM, Seger AC, So JW, Cook EF et al. An evaluation of risk factors for adverse drug events associated with angiotensin-converting enzyme inhibitors. J Eval Clin Pract. 2004;10:499-509. PubMed
  12. Vasotec (enalapril maleate). DailyMed [www]. US National Library of Medicine. [updated 2010-06-01, cited 2013-10-28]. länk
  13. Cherney DZ, Sochett EB, Miller JA. Gender differences in renal responses to hyperglycemia and angiotensin-converting enzyme inhibition in diabetes. Kidney Int. 2005;68:1722-8. PubMed
  14. Fischer M, Baessler A, Schunkert H. Renin angiotensin system and gender differences in the cardiovascular system. Cardiovasc Res. 2002;53:672-7. PubMed
  15. Boman KO, Jansson JH, Nyhlén KA, Nilsson TK. Improved fibrinolysis after one year of treatment with enalapril in men and women with uncomplicated myocardial infarction. Thromb Haemost. 2002;87:311-6. PubMed
  16. Pillans PI, Coulter DM, Black P. Angiooedema and urticaria with angiotensin converting enzyme inhibitors. Eur J Clin Pharmacol. 1996;51:123-6. PubMed
  17. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2015 [cited 2016-04-05.] länk

Författare: Linnéa Karlsson Lind, Desirée Loikas

Faktagranskat av: Mia von Euler

Godkänt av: Karin Schenck-Gustafsson